Reaction mass of (4Z)-4-ethylidene-2-propoxycyclohexanol and (4E)-4-ethylidene-2-propoxycyclohexanol and (5Z)-5-ethylidene-2-propoxycyclohexanol and (5E)-5-ethylidene-2-propoxycyclohexanol

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

Based on the absence of adverse effects on male and female fertility and reproductive performance, the NOAEL was determined to be ≥15000 mg/kg diet corresponding to an intake of at least 894 mg/kg body weight per day in females and at least 870 mg/kg body weight per day in males.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Additional information

In a GLP compliant study performed according to OECD guideline 422, the possible effects of the test substance on general toxicity and reproductive performance and development of pups were examined in groups of 12 male and 12 female Wistar rats. The test substance was administered at constant concentrations in the diet at levels of 0 (control), 1500, 5000 and 15000 mg/kg diet during a premating period of 2 weeks and during mating, gestation until day 4 of lactation. These dietary levels provided an overall mean intake of at least 104, 333 and 894 mg/kg body weight per day in females of the low-, mid- and high-dose group and at least 85, 280 and 870 mg/kg body weight per day in males of the low-, mid- and high-dose group.

 

The content and homogeneity of the test substance in the carrier were analysed and accepted. Stability testing showed a decrease in concentration after storage of the test substance in the carrier in the freezer for more than 5 weeks and slightly lower concentrations in the mid dose group after 4 days in the animal room. There was no treatment-related mortality. Daily clinical observations did not reveal any treatment-related clinical signs. Neurobehavioral observations and motor activity assessment did not indicate any neurotoxic potential of the test substance. There were no relevant differences in body weights or food consumption during the premating period, during the post-mating period in males, or in dams during the gestation period and the lactation period.

 

Hematology and clinical chemistry was conducted in 5 rats/sex/group at the end of the premating period. No effects were observed on hematology parameters. In males and females of the high-dose group phospholipids were increased compared to controls, glucose plasma levels were decreased in females of the high-dose group and liver weight was increased in males of the high-dose group. In absence of macroscopic and microscopic changes, these effects were considered treatment-related, but not adverse. Macroscopic/ Microscopic examination revealed no treatment-related effects. There were no effects of the test substance on fertility and reproductive performance.

 

Because fertility parameters, reproductive performance and development were not affected by the test substance, the NOAEL for reproduction and developmental effects was placed at ≥ 15000 mg/kg diet (the highest concentration tested; equivalent to an overall intake of at least 894 mg/kg bw/d in females and at least 870 mg/kg bw/d in males).

Justification for classification or non-classification

Based on the results of the combined oral repeated dose toxicity study and reproduction/developmental toxicity screening test, the test substance does not have to be classified for reproduction toxicity in accordance with Regulation (EC) No. 1272/2008.